As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

As one of the most common malignant tumors， digestive system tumors exhibit an increase in the incidence and mortality year by year. Its pathogenesis is complex， making it difficult to carry out early prevention. Autophagy is a process in which cells use lysosomes to degrade their organelles and macromolecules to maintain cellular homeostasis under the regulation of autophagy-related genes. Cellular autophagy has a dual regulatory effect on the tumor microenvironment， which always affects the occurrence and development of digestive system tumors. Therefore， the effect and mechanism of action of cellular autophagy on digestive system tumors have become a hot topic in tumor therapy in recent years. Meanwhile， the remarkable research results of targeted autophagy drugs indicate that cellular autophagy may become an important target for anti-digestive system tumors. Traditional Chinese medicine （TCM） has been widely used in the comprehensive treatment of digestive system tumors with good efficacy. A variety of active ingredients in TCM， such as flavonoids， glycosides， terpenoids， quinones， and alkaloids， can increase the expression of autophagy-associated proteins microtubule-associated protein 1 light chain 3 （LC3）Ⅱ/Ⅰ， autophagy-related gene （ATG）5， ATG7， inhibit the expression of autophagy-related protein p62 ， and induce autophagy in digestive system tumor cells， thereby exerting the anti-digestive system tumor effect. By summarizing the research results in recent years on the modulation of cell autophagy by active ingredients in TCM to fight against digestive system tumors， this paper analyzed the relevant signaling pathways， regulatory factors， and functional characteristics of cell autophagy modulation， so as to elucidate the mechanism by which active ingredients of TCM induce autophagy and to provide ideas and references for clinical application.

ObjectiveTo investigate the effect of interfering with long noncoding RNA （LncRNA） small nucleolar RNA host gene16 （SNHG16） on improving angiogenesis of ectopic endometrial stromal cells （EScs） in adenomyosis （AM） by targeting upregulation of miRNA （miR）-141-3p and inhibition of high mobility group box-1 protein （HMGB1）. MethodsThe expression levels of SNHG16， miR-141-3p and HMGB1 mRNA in endometrial tissues of 52 patients with adenomyosis （AM group） and 52 patients who needed hysterectomy due to cervical cancer or ovarian cancer （control group） were detected by quantitative reverse transcription polymerase chain reaction （qRT-PCR）. Y14 cells were divided into small hairpin RNA （shRNA） NC group， shRNA SNHG16 group， shRNA SNHG16+miR-141-3p inhibitor （inhibitor） group， shRNA SNHG16+inhibitor NC group and blank group. The targeting relationship between miR-141-3p and SNHG16 as well as HMGB1 was verified. The expression levels of SNHG16， miR-141-3p and HMGB1 mRNA in Y14 cells were detected by qRT-PCR. CCK-8 and Transwell assay were used to detect cell proliferation， invasion and migration. Microvascular density （MVD） was determined by immunofluorescence. The expressions of hypoxia-inducing factor α （HIF-1α）， cyclooxygenase-2 （Cox-2）， vascular endothelial growth factor （VEGF） and HMGB1 were detected by Western blot. ResultsThe expression of SNHG16 and HMGB1 mRNA in AM group was higher than that in control group， but the expression of miR-141-3p was lower than that in control group （P0.05）. The expression of SNHG16， HMGB1 mRNA， proliferation rate， migration， invasion number， MVD， expression of VEGF， HIF-1 α， Cox-2， and HMGB1 proteins in the shRNA SNHG16 group were lower than those in the blank group and shRNA NC group， while the expression of miR-141-3p was higher than that in the blank group and shRNA NC group （P0.05）. Inhibition of miR-141-3p reversed the improvement of EScs angiogenesis by interfering with SNHG16. ConclusionInterference with LncRNA SNHG16 improves EScs angiogenesis and inhibits proliferation， migration， and invasion of EScs by targeting upregulation of miR-141-3p and inhibition of HMGB1.

Objective To explore the application value of energy spectrum CT quantitative analysis in the diagnosis of malignant thyroid nodules and evaluation of cervical lymph node metastasis.Methods A total of 100 patients with thyroid nodules screened by ultrasound were selected as the study subjects.They were divided into the benign group(n=42)and the malignant group(n=58)according to pathological results.Patients in the malignant group were sub-divided into the metastasis group(n=26)and the non-metastasis group(n=32)according to the presence or absence of cervical lymph node metastasis.All patients received energy spectrum CT examination.The iodine concentration(IC),normalized iodine concentration(NIC)and the slope of the spectral Hounsfield unit curve(λHU)were measured.The receiver operating characteristic(ROC)curve was used to analyze the application value of energy spectrum CT quantitation in diagnosing malignant thyroid nodules and evaluating cervical lymph node metastasis.Results There were statistically significant differences in CT features(shape,edge,cystic changes and surrounding tissue invasion)between benign and malignant thyroid nodules(P＜0.05).However,there were no statistically significant differences in the maximum diameter,number,enhancement degree and calcification(P＞0.05).IClesion,NIC and λHU were lower in the benign group than those of the malignant group.IClesion,NIC and λHU of the metastasis group were lower than those of the non-metastasis group(P＜0.05).ROC curve analysis results showed that the AUCs,specificity,sensitivity and Youden index of the combination of IClesion,NIC and λHU for diagnosing malignant thyroid nodules and evaluating cervical lymph node metastasis were higher than those of each parameter(P＜0.05).Conclusion Energy spectrum CT quantitative analysis is of high value in the diagnosis of malignant thyroid nodules and evaluation of cervical lymph node metastasis.

Objective:To explore the effect of psoas muscle index (PMI) and construct a machine learning model to validate the 180-day prognosis in patients with decompensated liver cirrhosis.Methods:Retrospective data were collected from patients with decompensated liver cirrhosis at Henan Provincial People's Hospital from January 2022 to November 2022. The area of the psoas muscle index (PMI) at the level of the third lumbar vertebra was measured and calculated based on the abdominal X-ray computed tomography images stored in the Eastern China Hospital Information System (HIS). Patients were divided into low PMI and normal PMI groups according to the receiver operating characteristic curve. Patients clinical data and complication status were collected.The general conditions of both groups were compared using a t-test, chi-square test, and Mann-Whitney U test. The Kaplan-Meier method was applied for survival analysis. The outcome variable was 180-day mortality, and variables were selected using Cox and LASSO regression. The dataset was divided into training and testing sets in a 7∶3 ratio. Machine learning algorithms were used to build models in the training set, and model performance was validated by the test set. The model for MELD-Na score was compared with the model for End-Stage Liver Disease score. Results:A total of 298 patients with decompensated liver cirrhosis were included.The MELD scores, Child-Pugh classification, and NRS2002 scores, along with the incidence rate of complications such as ascites, hepatic encephalopathy, infections, and gastrointestinal bleeding, were significantly higher in the low PMI than the normal PMI group, with statistically significant differences ( P<0.05). The area under a receiver operating characteristic curve for the extreme gradient boosting model was higher than traditional clinical scores (MELD score 0.658, MELD_Na score 0.719) in the machine learning model. Furthermore, the application of SHAP results model indicated that PMI, hemoglobin, NRS2002 score, direct bilirubin, and blood ammonia were important factors in predicting the prognosis of patients with decompensated liver cirrhosis. Conclusion:A low PMI is closely related to poorer survival rates and the development of complication rates in patients with decompensated liver cirrhosis. The machine learning prediction model based on this construction, especially extreme gradient boosting, has favorable predictive performance, which is superior to the traditional clinical scoring system and can provide patients with the most accurate risk assessment and individualized treatment plan.

Objective The purpose of this study is to investigate the expression of histone lysine-specific demethylase 1 (KDM1A) and ubiquitin carboxyl-terminal hydrolase L3 (UCHL3) in thyroid cancer (TC) tissue and its relationship with clinical features and prognosis. Methods 94 TC patients diagnosed and treated at the Third Hospital of Heilongjiang Province from January 2017 to January 2019 were retrospectively selected as the study subjects. Immunohistochemistry was used to detect the expression of KDM1A and UCHL3 in tissues. Spearman correlation analysis was used to investigate the correlation between KDM1A and UCHL3. Kaplan-Meier survival curve was used to analyze the relationship between the levels of KDM1A and UCHL3 and the 5-year progression-free survival rate of TC patients. Multivariate COX regression model was used to analyze the prognostic factors of TC patients. Results The positive rates of KDM1A (68.09％) and UCHL3 (65.96％) in cancer tissues were higher than those in adjacent tissues(10.64％,8.51％),and the differences were statistically significant(x2=64.984,66.369,all P<0.001). The protein expression of KDM1A and UCHL3 was significant protein correlation (r=0.714,P<0.001). The positive rates of KDM1A (87.50％,90.91％) and UCHL3 (85.00％,87.88％) in TNM stage Ⅲ～Ⅳ and lymph node metastatic TC cancer tissues were higher than those in stage Ⅰ～Ⅱ(53.70％,53.85％)and non-lymph node metastatic(55.74％,54.10％) cancer tissues,and the differences were statistically significant(x2=9.985～12.191,all P<0.001). The 5-year progression-free survival rates of TC patients in the KDM1A positive and negative groups were 62.50％ (40/64) and 86.67％ (26/30),with significant differences,the 5-year progression-free survival rates of UCHL3 positive and negative patients were 58.06％ (36/62) and 90.63％ (29/32),with significant differences (Log-Rankx2=5.670,9.724,P=0.017,0.002). KDM1A positive,UCHL3 positive,TNM stage Ⅲ～Ⅳ,lymph node metastasis were risk factors affecting the prognosis of TC patients (Waldx2=1.315～1.697,all P<0.001). Conclusion KDM1A and UCHL3 are upregulated in TC,and played a pro-cancer role. They are new tumor markers for evaluating the prognosis of TC patients.

Objective To investigate the relationship between plasma von willebrand factory-lytic protease (ADAMTS13) level and the severity of the disease and its prognostic value in patients with endometriosis (EMS). Methods 130 patients with EMS treated in the hospital from January 2019 to December 2022 were retrospectively selected. Plasma ADAMTS13 level was detected by enzyme-linked immunosorbent assay (ELISA),and its correla-tion with American Fertility Society (r-AFS) stage and endometriosis Health Status Scale (EHP-30) score was analyzed. The 1-year prognosis was recorded,and the risk factors of poor prognosis were analyzed by logistic regression. Receiver operating characteristic curve (ROC) was plotted to evaluate the predictive value of plasma ADAMTS13 levels in patients with EMS. Results The plasma ADAMTS13 level of EMS patients decreased signifi-cantly with the increase of r-AFS stage,and was negatively correlated with the score of EHP-30 (P<0.001). Multiple factors showed that low plasma ADAMTS13 level,bilateral location of pelvic lesions and high r-AFS stage were independent risk factors for poor prognosis (all P<0.05). ROC analysis showed that the area under the curve (AUC) of plasma ADAMTS13 was 0.889 (cut-off point 13.315,sensitivity 0.931,specificity 0.690). Conclusion Plasma ADAMTS13 level is negatively correlated with the severity of EMS,and is an independent risk factor for poor prognosis of EMS patients,and has a certain predictive value for prognosis of EMS patients.

Although cancer immunotherapy has made great strides in the clinic, it is still hindered by the tumor immunosuppressive microenvironment (TIME). The stimulator of interferon genes (STING) pathway which can modulate TIME effectively has emerged as a promising therapeutic recently. However, the delivery of most STING agonists, specifically cyclic dinucleotides (CDNs), is performed intratumorally due to their insufficient pharmacological properties, such as weak permeability across cell membranes and vulnerability to nuclease degradation. To expand the clinical applicability of CDNs, a novel pH-sensitive polycationic polymer-modified lipid nanoparticle (LNP-B) system was developed for intravenous delivery of CDNs. LNP-B significantly extended the circulation of CDNs and enhanced the accumulation of CDNs within the tumor, spleen, and tumor-draining lymph nodes compared with free CDNs thereby triggering the STING pathway of dendritic cells and repolarizing pro-tumor macrophages. These events subsequently gave rise to potent anti-tumor immune reactions and substantial inhibition of tumors in CT26 colon cancer-bearing mouse models. In addition, due to the acid-sensitive property of the polycationic polymer, the delivery system of LNP-B was more biocompatible and safer compared with lipid nanoparticles formulated with an indissociable cationic DOTAP (LNP-D). These findings suggest that LNP-B has great potential in the intravenous delivery of CDNs for tumor immunotherapy.

Microglial pyroptosis and neuroinflammation have been implicated in the pathogenesis of sepsis-associated encephalopathy (SAE). OGT-mediated O-GlcNAcylation is involved in neurodevelopment and injury. However, its regulatory function in microglial pyroptosis and involvement in SAE remains unclear. In this study, we demonstrated that OGT deficiency augmented microglial pyroptosis and exacerbated secondary neuronal injury. Furthermore, OGT inhibition impaired cognitive function in healthy mice and accelerated the progression in SAE mice. Mechanistically, OGT-mediated O-GlcNAcylation of ATF2 at Ser44 inhibited its phosphorylation and nuclear translocation, thereby amplifying NLRP3 inflammasome activation and promoting inflammatory cytokine production in microglia in response to LPS/Nigericin stimulation. In conclusion, this study uncovers the critical role of OGT-mediated O-GlcNAcylation in modulating microglial activity through the regulation of ATF2 and thus protects against SAE progression.
Animals ; Microglia/metabolism* ; Pyroptosis/physiology* ; Mice ; Sepsis-Associated Encephalopathy/prevention & control* ; Activating Transcription Factor 2/metabolism* ; N-Acetylglucosaminyltransferases/genetics* ; Mice, Inbred C57BL ; Male ; Mice, Knockout

Objective To provide methodological examples for related research,the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease(COPD)based on a nonlinear mixed effects model was explored.Methods A research questionnaire on the influencing factors of the evolution of Qi deficiency syndrome in chronic obstructive pulmonary disease was developed,and clinical data of 650 COPD patients on the 1st and 14th day of acute exacerbation,the 1st and 28th day of risk window,the first day of stable period,and the 90th day were dynamically collected from 10 tertiary hospitals across the country.8 baseline data including gender and age were collected through the PROC NLMIXED process by SAS 9.4 software.Coronary heart disease,diabetes and hypertension accounted for the highest proportion.Nine concurrent syndromes including wind cold syndrome and phlegm heat syndrome were used as fixed effects,and individual level was used as random effects to gradually fit the model and screen the influencing factors of Qi deficiency syndrome in the entire process of disease occurrence and development.Results A total of 637 eligible cases were included,and clinical datas were dynamically collected on the 1st and 14th day of acute exacerbation,the 1st and 28th day of the risk window,the 1st and 90th day of the stable period.It was found that the number of acute exacerbations,alcohol consumption,concomitant hypertension,coronary heart disease,blood stasis syndrome,yin deficiency syndrome,yang deficiency syndrome,6-minute walking distance,and the modified Medical Research Council Dyspnea Questionnaire(mMRC)had an impact on the evolution of Qi deficiency syndrome in the previous year(P<0.05).Conclusion The use of a nonlinear mixed effects model revealed the relevant factors affecting the evolution of Qi deficiency syndrome from complex multi temporal dynamic data,providing methodological references for other related studies.